Elastography is a noninvasive, ultrasound image technique that provides objective data to evaluate tissue elasticity or stiffness by measuring tissue displacement using compression. The technique employs external compression in order to induce strain inside the tissue that is scanned. Tissue compression produces strain or displacement within the tissue; therefore, the strain is smaller and harder in the malignant tissue than in the benign tissue. By measuring the tissue strain, tissue hardness can be estimated differentiating between malignant and benign masses. The resulting strain image is called an elastogram. Each pixel on the elastogram denotes the estimated amount of strain the tissue experienced during the applied compression. Clinical use of elastography is increasing, with applications including lesion detection and classification, fibrosis staging, treatment monitoring, vascular imaging and musculoskeletal applications. (1, 2)

Elastography may be useful but it is not commonly used clinically. The concern is that obesity can decrease the diagnostic accuracy which would potentially limit the usefulness of the test especially in countries where obesity and metabolic syndrome are common. (3)

There are several types of ultrasound elasticity imaging:

Elastography: Tracks tissue movement during compression to obtain an estimate of strain,

Sonoelastography (SE): Evaluates reproducible differences in backscattered ultrasound signals that result from compression of tissues and uses color doppler to generate an image of tissue movement in response to the external vibrations,

Shear Wave Elastography (SWE): Uses focused beams of ultrasound energy from conventional transducers to produce movement within several microns at depths up to six centimeters below the ultrasound transducer. The technique results in low frequency shear waves in a plane perpendicular to tissue displacement. The speed of shear wave propagation is directly proportional to tissue elasticity, with faster speeds in tissue stiffness. Data is displayed in kilopascals (kPa) on color coded elasticity maps.

MR Elastography (MRE): A pneumatic driver is activated by a special MRE pulse sequence that performs velocity encoding through phase sensitization. The pulse sequence is sensitive to the transmission of waves through the tissue, and the data from the troughs and peaks is mathematically converted into parametric images that display tissue elasticity in kPa. (4)

The Food and Drug Administration (FDA) approved the diagnostic ultrasound system (Elastography combined B/M-mode) under 510(K) (K132341) on May 22, 2013. This elastography device employs an array of probes that include linear array, convex array, and phased array with a frequency range of approximately 3- 10.0MHz. This device is applicable

The FDA approved the Acoustic Radiation Force Impulse (ARFI) in 2013. This technology is cleared for abdominal, breast, thyroid, and musculoskeletal exams. It precisely focuses the ultrasound beam within the region of interest as it enhances a lesions border and size. (17)

Policy

Each benefit plan, summary plan description, or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description, or contract will govern.

Coverage

Elastography, by any method, is considered experimental, investigational, and/or unproven.

Rationale

Liver

Several studies have recently been published regarding elastography to diagnosis and evaluate liver conditions. Leung, et al. (2013) studied SWE for assessing liver fibrosis in chronic hepatitis B and compared its performance with transient elastography (TE). The study analyzed 226 patients with liver biopsy correlation and 171 healthy patients. SWE of liver, TE of liver, and SWE of spleen was 0.86, 0.80, and 0.81 for fibrosis (≥F1 stage); 0.88, 0.78, and 0.82 for moderate fibrosis (≥F2 stage); 0.93, 0.83, and 0.83 for severe fibrosis (≥F3 stage); and 0.98, 0.92, and 0.84 for cirrhosis (F4 stage). SWE of the liver showed significantly higher accuracy than TE of liver and SWE of the spleen in all fibrosis stages. SWE of the spleen showed similar accuracy with TE of liver. Combination SWE of liver and spleen to predict fibrosis staging showed diagnostic accuracy which was not improved compared with SWE of the liver alone. SWE of the liver had a higher success rate than TE of liver (98.9% vs 89.6%). Prevalence of discordance in at least two stages with liver histologic staging was 10.2% (23 of 226) for SWE of the liver and 28.2% (58 of 206) for SWE of the spleen. It was determined that SWE provides more accurate correlation of liver elasticity with liver fibrosis stage compared with TE, especially in identification of stage F2 or greater. (5)

Cassinotto et.al completed a study of 321 patients with chronic liver disease who underwent liver biopsies from April 2010 to May 2012 to compare the diagnostic performance of acoustic radiation force impulse (ARFI) elastography with that of FibroScan (Â®) M and XL probes and FibroTest in the staging of fibrosis in patients with chronic liver disease. Liver disease was caused by viral hepatitis (n = 136), alcoholic or nonalcoholic steatohepatitis disorders (n = 113), or some other disease (n = 72). In each patient, liver stiffness was evaluated with ARFI elastography, M and XL probes, and FibroTest was done within 1 month prior to liver biopsy. Histologic staging of liver fibrosis served as the reference standard. Liver stiffness measurement failure rates were 11.2% with the M probe (36 of 321 patients), 2.3% with the XL probe (6 of 260 patients), and 0% with ARFI elastography (0 of 321 patients). Unreliable results with ARFI elastography were more frequent in obese patients (those with a body mass index of 30 kg/m2 or more) (42 of 86 patients [48.8%] vs 34 of 235 patients. No significant difference was found between ARFI elastography and the M probe in the diagnosis of cirrhosis (area under the receiver operating characteristic curve, or severe fibrosis; however, the M probe demonstrated better results in the diagnosis of moderate fibrosis. No significant difference was found between ARFI elastography and the XL probe in the diagnosis of moderate fibrosis, severe fibrosis, or cirrhosis. The diagnostic performance of ARFI elastography improved when it was applied in nonobese patients (Az of ARFI for cirrhosis and severe fibrosis = 0.92 and 0.91, respectively, in nonobese patients [P = .0002] and 0.63 and 0.63, respectively, in obese patients [P < .0001]). The authors determined that ARFI elastography is reliable in the assessment of liver fibrosis in patients with chronic liver disease, especially nonobese patients. (6)

Potthoff et. al (2013) studied the influence of different frequencies and insertion depths on the diagnostic accuracy of liver elastography by ARFI imaging. ARFI is an innovative elastography for staging of liver fibrosis. Diagnostic accuracy of different probes was evaluated at different insertion depths. This was a prospective study, 89 chronic HCV infected patients underwent ARFI elastography using both available probes (c-ARFI: C4-1-MHz; l-ARFI: L9-4 MHz) in comparison to Fibroscan (Â®). Variability of ARFI elastography at different insertion depths was systematically evaluated in 39 patients (44%). According to Fibroscan (Â®) elastography, 32 patients (36%) presented with liver cirrhosis, 23 patients (26%) had significant fibrosis, and 34 patients (38%) had no significant fibrosis. Results of both probes were correlated to each other and to Fibroscan (Â®). In patients with significant fibrosis or with cirrhosis, mean values by 1-ARFI were significantly higher than by c- ARFI. For detection of liver cirrhosis, AUROC was 0.97 for c-ARFI (cut-off level 1.72m/s) and 0.90 for l-ARFI (cut-off 2.04m/s). Correlation coefficients of c-ARFI with Fibroscan (Â®) were highest at an insertion depth of 5-6cm and at 3-4cm for l-ARFI. It was determined, ARFI elastography with the linear probe verses the convex probes showed comparable validity and accuracy in the estimation of liver stiffness. The linear probe gave higher ARFI values. The most accurate insertion depth was 5-6cm for c-ARFI and 3- 4cm for l-ARFI indicating that measurements should not be performed close to the liver capsule. (7)

Sirli, R, et al. (2013) completed a retrospective study to assess the feasibility of TE and the factors associated with failed and unreliable liver stiffness measurements (LSMs), in patients with chronic liver diseases. 8218 consecutive adult patients with suspected chronic liver diseases were included. In each patient, LSMs were performed with a FibroScan (Â®) device (Echosens, France), with the M probe. Failure of TE measurements was defined if no valid measurement was obtained after at least 10 shots and unreliable if fewer than 10 valid shots were obtained.

From the 8218 patients, failed and unreliable LSMs were observed in 29.2% of cases. In univariant analysis, the following risk factors were associated with failed and unreliable measurements: age over 50 years, female gender, BMI>27.7kg/m, weight>77kg, and height<162cm. In multivariate analysis all the factors mentioned were independently associated with the risk of failed and unreliable measurements. If all the negative predictive factors were present (woman, older than 50 years, with BMI>27.7kg/m, heavier than 77kg and shorter than 162cm), the rate of failed and unreliable measurements was 58.5%. In obese patients, the rate of failed and unreliable measurements was 49.5%. Failed and unreliable LSMs were observed in 29.1% of patients. Female gender, older age, higher BMI, higher weight, and smaller height were significantly associated with failed and unreliable LSMs. (8)

Kim et al. (2013) evaluated the diagnostic accuracy of MRE as a method to help diagnose clinically substantial fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) and, by using MRE as a reference standard, to compare various laboratory marker panels in the identification of patients with NAFLD and advanced fibrosis. This retrospective study involved 325 patients with NAFLD, who were identified by imaging characteristics consistent with steatosis in a prospective database that tracks all MRE examinations. Six laboratory-based models of fibrosis were compared with MRE results as well as fibrosis stage from liver biopsy results. The area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, positive predictive value, and negative predictive value of each data set were compared. Among 325 patients with NAFLD with MRE data, there were 142 patients who underwent liver biopsy within 1 year of MRE. When comparing MRE results with liver biopsy results, the best cutoff for advanced fibrosis (stage F3–F4, 46 [32.4%] of 142) was 4.15 kilopascals (AUROC = 0.954, sensitivity = 0.85, specificity = 0.929). This cutoff value identified 104 patients with advanced fibrosis (32.0% of 325 patients). The FIB-4 score (AUROC = 0.827) and NAFLD fibrosis score (AUROC = 0.821) had the best diagnostic accuracy for advanced fibrosis, with high negative predictive values (NAFLD fibrosis score = 0.90 and FIB-4 score = 0.899). In Conclusion, MRE is a useful diagnostic tool for detecting advanced fibrosis in NAFLD. Of the laboratory-based methods, the NAFLD fibrosis and FIB-4 scores can most reliably detect advanced fibrosis. (9)

Thyroid

Sebag et al. (2010) used SWE and conventional ultrasound to evaluate thyroid nodules in 93 patients; 61 patients had a solitary nodule and 32 had multiple nodules. Subclinical hyperthyroidism was found in 5 patients and subclinical hypothyroidism in 3; 79 patients had thyroid surgery, including all of those with multinodular goiter and 47 of the 61 with single nodules. There was an additional control group with normal thyroid function who underwent ultrasonography and elastography. (The authors did not state whether fine-needle aspiration (FNA) of the nodules was performed.) The ultrasound device used in the study was developed by Supersonic Image (Les Jardins de la Duranne, Aix-en-Provence, France). It uses pushing beams to generate a shear wave and then calculates an elasticity index in kilopascals (kPa). It also displays an image in which softer tissue is blue and stiffer tissue is red.

In conclusion, fifteen of the solitary nodules were malignant and 8 of those with multinodular goiter had 14 separate carcinomas. The ultrasound features predictive of malignancy were hypoechogenicity (sensitivity, 70%; specificity, 82%), absent halo sign (sensitivity, 93%; specificity, 41%), microcalcifications (sensitivity, 67%; specificity, 85%), and intra nodular vascularity (sensitivity, 52%; specificity, 94%). The presence of dense macro calcifications >2 mm was not predictive of malignancy, with a sensitivity of 22% and a specificity of 79.6%.

The mean (±SD) elasticity index was significantly higher in malignant nodules (150±95 kPa [95% confidence interval {CI}, 30 to 356]) than in benign nodules (36±30 [95% CI, 0 to 200]) and normal thyroid glands (15.9±7.6 [95% CI, 5 to 35]) (P<0.001). For a positive predictive value of at least 80%, the cutoff level of the elasticity index for malignancy was estimated as 65 kPa. The elasticity index was <65 kPa (negative) in three papillary thyroid carcinomas and one follicular tumor of uncertain malignant potential. It was >65 kPa in all follicular carcinomas and in the one medullary and one anaplastic carcinoma. SWE is recommended as the first-line procedure for evaluation of thyroid nodules. When the value is >65 kPa, FNA should be performed, and if <65 kPa, the decision for FNA may be based on other ultrasound characteristics. (10)

In March 2013, Moon et al. evaluated the diagnostic performance of gray-scale ultrasound and elastography in differentiating benign and malignant thyroid nodules. This was an institutional review board–approved retrospective study. A total of 703 solid thyroid nodules in 676 patients (mean age, 49.7 years; range, 18–79 years) were included; there were 556 women (mean age, 49.5 years; range, 20–74 years) and 120 men (mean age, 50.7 years; range, 18–79 years). Nodules with marked hypoechogenicity, poorly defined margins, microcalcifications, and a taller-than-wide shape were classified as suspicious at grayscale ultrasound. Findings at elastography were classified according to the Rago criteria and the Asteria criteria. The diagnostic performances of gray-scale ultrasound and elastography were compared. For comparison between the diagnostic performances of gray-scale Ultrasound and the combination of gray-scale Ultrasound and elastography, three sets of criteria were assigned: criteria set 1, nodules with any suspicious grayscale Ultrasound feature were assessed as suspicious; criteria set 2, Rago criteria were added as suspicious features to criteria set 1; and criteria set 3, Asteria criteria were added as suspicious features to criteria set 1. The diagnostic performances of gray-scale Ultrasound elastography with Rago criteria, and elastography with Asteria criteria, and odds ratios (ORs) with 95% confidence intervals for predicting thyroid malignancy were compared using generalized estimating equation analysis. Of 703 nodules, 217 were malignant and 486 were benign. Sensitivity, negative predictive value (NPV), and OR of gray-scale ultrasound for the 703 nodules were 91.7%, 94.7%, and 22.1, respectively, and these values were higher than the 15.7% and 65.4% sensitivity, 71.7% and 79.1% NPV, and 3.7 and 2.6 ORs found for elastography with Rago and Asteria criteria, respectively. Specificity, positive predictive value, and accuracy for criteria set 1 were significantly higher than those for criteria sets 2 and 3 for most of the nodule subgroups that were considered. Elastography alone, as well as the combination of elastography and gray-scale Ultrasound, showed inferior performance in the differentiation of malignant and benign thyroid nodules compared with gray-scale US features; elastography was not a useful tool in recommending fine-needle aspiration biopsy. (11)

Breast

Kumm and Szabunio (2010) evaluated the application and diagnostic performance of elastography for the characterization of breast lesions in patients referred for biopsy. Subjects referred for ultrasound-guided biopsy of sonographically apparent breast lesions were included in this study. The Hitachi Hi-Vision 900 ultrasound® was used to generate index test results for elastography scoring (ES) and for strain ratio (SR) measurement. Sensitivity, specificity, PPV and NPV were determined using pathologic results from 14-gauge core needle biopsy as the reference standard. A total of 310 lesions in 288 patients were included in this study. Out of 310 lesions, 223 (72 %) were benign and 87 (28 %) were malignant. Sensitivity was 0.76 for ES and 0.79 for SR. Specificity was 0.81 for ES and 0.76 for SR. The PPV was 0.60 for ES and 0.57 for SR; the NPV was 0.90 for ES and 0.90 for SR. The SR values for malignant lesions were significantly higher (median ratios of 10.5 and 2.7, respectively, p < 0.001). The authors concluded that while the initial clinical performance of elastography imaging shows potential to reduce biopsy of low-risk lesions, a large-scale trial addressing appropriate patient selection, diagnostic parameters, and practical application of this technique is needed before widespread clinical use. (12)

Cho and colleagues (2011) investigated the effect of the combined use of ultrasonographic (US) elastography and color Doppler US on the accuracy of radiologists in distinguishing benign from malignant nonpalpable breast masses and in making the decision for biopsy recommendations at B-mode US. A prospective study was conducted with a cohort of 367 biopsy-proved cases in 319 women (age range, 22–78 years; mean age, 48.6 years) with B-mode US, US elastographic, and Doppler US images was included Five blinded readers independently scored the likelihood of malignancy for four data sets (i.e., B-mode US alone, B-mode US and elastography, B-mode US and Doppler US, and B-mode US, US elastography, and Doppler US). The area under the receiver operating characteristic curve (A z) values, sensitivities, and specificities of each data set were compared. The A z of B-mode US, US elastography, and Doppler US (average, 0.844; range, 0.797–0.876) was greater than that of B-mode US alone (average, 0.771; range, 0.738–0.798) for all readers ( P = .001 for readers 1, 2, and 3; P , .001 for reader 4; P = .002 for reader 5). When both elastography and Doppler scores were negative, leading to strict downgrading, the specificity increased for all readers from an average of 25.3% (75.4 of 298; range, 6.4%–40.9%) to 34.0% (101.2 of 298; range, 26.5%–48.7%) (P, .001 for readers 1, 2, 4, and 5; P = .016 for reader 3) without a significant change in sensitivity. The study determined the US elastography and color Doppler US increases both the accuracy in distinguishing benign from malignant masses and the specificity in decision-making for biopsy recommendation at B-mode US. (13)

Landoni and colleagues (2012) developed a quantitative method for breast cancer diagnosis based on elastosonography images in attempt to reduce unnecessary biopsies. The proposed method was validated by correlating the results of quantitative analysis with the diagnosis assessed by histopathologic examination. A total of 109 images of breast lesions (50 benign and 59 malignant) were acquired with the traditional B-mode technique and with elastographic modality. Images in Digital Imaging and Communications in Medicine format (DICOM) were exported into software, written in Visual Basic, especially developed to perform this study. The lesion was contoured and the mean grey value and softness inside the region of interest (ROI) were calculated. The correlations between variables were investigated and receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic accuracy of the proposed method. Pathologic results were used as standard reference. Both the mean grey value and the softness inside the ROI resulted statistically different at the t-test for the 2 populations of lesions (i.e., benign versus malignant): p <0.0001. The area under the curve (AUC) was 0.924 (0.834 to 0.973) and 0.917 (0.826 to 0.970) for the mean grey value and for the softness respectively. The authors concluded that quantitative elastosonography is a promising ultrasound technique in the detection of breast cancer; but large prospective trials are needed to determine if quantitative analysis of images can help to overcome some pitfalls of this method. (14)

In 2013 Park et al. compared observer variability between lexicons and final categorization of Breast Imaging and Data System (BI-RADS) and the elasticity score of US elastography. From April 2009 to February 2010, 1356 breast lesions in 1330 patients underwent ultrasound-guided core biopsy. Among them, 63 breast lesions in 55 patients (mean age, 45.7 years; range, 21-79 years) underwent both conventional ultrasound and elastography and were included in this study. Two radiologists independently performed conventional ultrasound and elastography, and another three observers reviewed conventional ultrasound images and elastography videos. Observers independently recorded the elasticity score for a 5-point scoring system proposed by Itoh et al., BI-RADS lexicons and final category using ultrasound BI-RADS. The histopathologic results were obtained and used as the reference standard. Interobserver variability was evaluated. Of the 63 lesions, 42 (66.7 %) were benign, and 21 (33.3 %) were malignant. The highest value of concordance among all variables was achieved for the elasticity score (k = 0.59), followed by shape (k = 0.54), final category (k = 0.48), posterior acoustic features (k = 0.44), echogenicity and orientation (k = 0.43). The least concordances were margin (k = 0.26), lesion boundary (k = 0.29) and calcification (k = 0.3). Elasticity score showed a higher level of interobserver agreement for the diagnosis of breast lesions than BI-RADS lexicons and final category. (15)

A literature search through October 2013 identified multiple studies to evaluate elastography technology for the use in various medical conditions to include the breast, thyroid, abdominal and musculoskeletal system. Although elastography appears promising as a diagnostic tool for the clarification of lesions and nodules, it is still in its early stages of research. Large scientifically controlled studies are needed in order to validate the diagnostic performance as compared to other diagnostic tests currently available.

Professional Organizations

The Association for Medical Ultrasound does not make a recommendation on elastography in their clinical practice guidelines. The National Comprehensive Cancer Network (NCCN) practice guidelines for colon cancer (version 2.2012), lobular carcinoma in Situ (version 1.2012), breast cancer screening, and diagnosis (version 3.2012) does not indicate elastography as a diagnostic modality in their clinical guidelines. (18, 19, 20)

Coding

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